1. Technical Field of the Invention
The present invention relates to a novel process for the preparation of optically active .alpha.-(hydroxyphenoxy) alkanecarboxylic acids, and, more especially, to the preparation of optically pure D-2-(4-hydroxyphenoxy)propionic acid (hereinafter also abbreviated to "D-HPPA" for purposes of simplicity).
This invention also relates to the preparation of optically active derivatives of the .alpha.-(hydroxyphenoxy)alkanecarboxylic acids, in particular to the optically active alkyl esters thereof.
2. Description of the Prior Art
Aliphatic esters of optically pure D-2-(4-hydroxyphenoxy)propionic acid are intermediates for selective herbicides which currently are in great demand.
These esters can be obtained directly via a Walden inversion from an alkyl L-chloro- or L-bromopropionate and hydroquinone, in the presence of a strong base, in an aqueous or alcoholic reaction medium. Unfortunately, in these media the esters are readily hydrolyzed and the chloropropionic moiety is racemized, as described by W. A. Cowdrey et al, Journal of the Chemical Society, 1208 (1937).
These esters can also be prepared from D-2-(4-hydroxyphenoxy)propionic acid. However, there are two principal differences in the preparation of D-2-(4-hydroxyphenoxy)propionic acid: (1) manufacturing a product with high optical purity and, (2) obtaining a monosubstituted hydroquinone compound with high selectivity.
D-HPPA is synthesized utilizing the processes described in the prior art, in an alcoholic or aqueous medium.
Thus, JP-A-62/16,446 describes the preparation of D-HPPA by reacting a sodium salt of L-.alpha.-chloropropionic acid, in ethanolic solution, with hydroquinone in the presence of caustic acid. The process described is carried out in an anhydrous medium. The sodium salt of the L-.alpha.-chloropropionic acid is obtained from the methyl ester of L-.alpha.-chloropropionic acid added to an aqueous solution of sodium hydroxide, followed by elimination of the water by reduced pressure distillation to provide a white solid which is recovered and dissolved in ethanol.
This process must be carried out in an anhydrous medium which is very restricting from an industrial viewpoint and handling the solid is not easy, as the substance is quite sticky.
D-HPPA can be prepared in an aqueous medium; the two references indicated above illustrate this preparative technique.
EP-B-0,108,374 describes a process for the preparation of hydroxyphenoxy-alkanecarboxylic acids, including 2-(4-hydroxyphenoxy)propionic acid.
The distinguishing characteristic of the '374 process is to mix dihydroxybenzene in an alkaline solution with a 2-halogeno-alkanecarboxylic acid (or halide or ester thereof) at a temperature of less than 60.degree. C., and then to continuously transfer the mixture through a tube reactor at temperatures of 80.degree. C. to 120.degree. C.
Monoalkylation is said to be obtained by the continuous passage of the reaction medium through the tube reactor for a short period of time, at a high temperature. This type of process requires specialized apparatus.
EP-A-0,192,849 describes the preparation of a derivative of an optically active (4-hydroxy-2-phenoxy)propionic acid, entailing reacting an alkaline salt of an optically active .alpha.-halogeno-propionic acid with dihydroxybenzene or an alkaline hydroquinone salt, in the presence of an alkali metal hydroxide and a suitable amount of water which will precipitate the disodium salt of the optically active (4-hydroxy-2-phenoxy)propionic acid. The water is employed in an amount such that the ratio of water/hydroquinone ranges from 1 to 2.5 by weight.